Activated Phosphoinositide 3-Kinase Delta Syndrome, APDS (NORD)

Activated Phosphoinositide 3-Kinase Delta Syndrome, also called APDS, is a rare syndrome characterized by the impaired growth, development, and function of lymphocytes. Lymphocytes are immune cells that protect the body from pathogens, like bacteria and viruses. B lymphocytes produce antibodies to fight infections, while T lymphocytes help to attack and destroy infected cells. In APDS, a genetic mutation, also called a pathogenic variant, causes both B and T lymphocytes to malfunction, which may lead to frequent infections, chronic lung disease, enlargement of lymphoid structures, like the lymph nodes, liver, and spleen, and autoimmune disorders. Individuals with APDS are also at an increased risk of malignant lymphoid disorders, like lymphomas.

APDS is caused by a gain-of-function mutation, also called an activating mutation, in the genes that encode phosphoinositide 3-kinase delta, also called PI3Kδ. PI3Kδ is a protein that plays an important role in lymphocyte  proliferation, survival, and activation.  APDS can be divided into two types. Type 1 is caused by a mutation in the PIK3CD gene, while Type 2 is caused by a mutation in the PIK3R1 gene. Both are inherited in an autosomal dominant manner, which means that patients need only one copy of the mutated gene for the disease to develop. The mutated gene can be inherited or occur for the first time in the affected individual.

Signs and symptoms of APDS typically present in early childhood. Although the clinical manifestations vary in range and severity, individuals typically present with frequent ear, sinus upper respiratory, and lung infections.

Individuals with APDS may also have swollen lymph nodes and an oversized liver or spleen. Other clinical findings may include hearing loss, permanent lung disease, chronic diarrhea, fatigue due to autoimmune anemia, easy bruising due to autoimmune thrombocytopenia, and lymphoma or other blood cancers.